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Published online on April 19, 2004, 10.1073/pnas.0308291101

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Medical Sciences
Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans

Luigi Fontana *{dagger}, Timothy E. Meyer *, Samuel Klein *, and John O. Holloszy *{ddagger}

*Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110; and {dagger}Division of Food Science, Human Nutrition and Health, Istituto Superiore di Sanitá, 00161 Rome, Italy

Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved March 16, 2004 (received for review December 12, 2003)

Little is known regarding the long-term effects of caloric restriction (CR) on the risk for atherosclerosis. We evaluated the effect of CR on risk factors for atherosclerosis in individuals who are restricting food intake to slow aging. We studied 18 individuals who had been on CR for an average of 6 years and 18 age-matched healthy individuals on typical American diets. We measured serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure (BP), high-sensitivity C-reactive protein (CRP), platelet-derived growth factor AB (PDGF-AB), body composition, and carotid artery intima-media thickness (IMT). The CR group were leaner than the comparison group (body mass index, 19.6 ± 1.9 vs. 25.9 ± 3.2 kg/m2; percent body fat, 8.7 ± 7% vs. 24 ± 8%). Serum total cholesterol (Tchol), low-density lipoprotein cholesterol, ratio of Tchol to high-density lipoprotein cholesterol (HDL-C), triglycerides, fasting glucose, fasting insulin, CRP, PDFG-AB, and systolic and diastolic BP were all markedly lower, whereas HDL-C was higher, in the CR than in the American diet group. Medical records indicated that the CR group had serum lipid-lipoprotein and BP levels in the usual range for individuals on typical American diets, and similar to those of the comparison group, before they began CR. Carotid artery IMT was {approx}40% less in the CR group than in the comparison group. Based on a range of risk factors, it appears that long-term CR has a powerful protective effect against atherosclerosis. This interpretation is supported by the finding of a low carotid artery IMT.

{ddagger}To whom correspondence should be addressed at: Washington University School of Medicine, Section of Applied Physiology, Campus Box 8113, 4566 Scott Avenue, St. Louis, MO 63110.

John O. Holloszy , E-mail: jhollosz{at}im.wustl.edu

www.pnas.org/cgi/doi/10.1073/pnas.0308291101
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